Cisplatin Nanoparticles Promote Intratumoral CD8+ T Cell Priming via Antigen Presentation and T Cell Receptor Crosstalk.
Nano Lett
; 22(8): 3328-3339, 2022 04 27.
Article
em En
| MEDLINE
| ID: mdl-35404605
ABSTRACT
Nanomedicines are highly promising for cancer therapy due to their minimal side effects. However, little is known regarding their host immune response, which may limit their clinical efficacy and applications. Here, we find that cisplatin (CDDP)-loaded poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol) complex nanoparticles (CDDP-NPs) elicit a strong antitumor CD8+ T cell-mediated immune response in a tumor-bearing mouse model compared to free CDDP. Mechanistically, the sustained retention of CDDP-NPs results in persistent tumor MHC-I overexpression, which promotes the formation of MHC-I-antigen peptide complex (pMHC-I), enhances the interaction between pMHC-I and T cell receptor (TCR), and leads to the activation of TCR signaling pathway and CD8+ T cell-mediated immune response. Furthermore, CDDP-NPs upregulate the costimulatory OX40 on intratumoral CD8+ T cells, and synergize with the agonistic OX40 antibody (aOX40) to suppress tumor growth by 89.2%. Our study provides a basis for the efficacy advantage of CDDP-based nanomedicines and immunotherapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cisplatino
/
Nanopartículas
Limite:
Animals
Idioma:
En
Revista:
Nano Lett
Ano de publicação:
2022
Tipo de documento:
Article